Is topiroxostat efficient in Japanese hyperuricemic patients including gout?
When there is surplus uric acid in the blood, this condition is termed as hyperuricemia. It is prevalent in the gout arthritis patients. In Japan, topiroxostat which is a selective xanthine oxidoreductase inhibitor, has been used for the treatment of patients with hyperuricemia including gout. But, till now there are no publication studies estimating the dose-dependent relationship with respect to the serum urate-lowering efficacy. Hence, here this criteria is being assessed along with the safety of topiroxostat in Japanese hyperuricemic patients including gout.
In Japanese hyperuricemic patients with or without gout, a exploratory, phase 2a, multicentre, randomized, double-blind, 8-week, placebo-controlled study was conducted. The study included the placebo and topiroxostat 40, 60, 80 or 120 mg /day. Primary efficacy endpoint showed the serum urate level change in percentage value.
Total 187 patients were randomized out of which 186 received at least one dose of study drug. The product obtained from the study had dose dependent serum urate reduction effect of 40 to 120 mg/day (P < 0·001, Jonckheere-Terpstra test). There was a difference of -32·4% ([95% confidence interval, -38·9% to -25·9%]; P < 0·001) in serum urate level as the mean percent change from baseline at the final visit was -30·8% in the 120-mg group and 1·6% with placebo. Statistically, the occurence of adverse effects (AE's) in the 120-mg group was lower than that in the placebo group. Overall AEs in the topiroxostat groups were comparable to those in the placebo group. Higher incidence of gouty arthritis was observed in topiroxostat 80- and 120-mg groups.
In Japanese hyperuricemic male patients with or without gout, dose-dependent serum urate lowering efficacy of topiroxostat was perceived. For the warranty of clinical efficacy and long term safety, clinical studies needs to be evaluated.